Recent evidence suggests that progressive tumor growth is accompanied by immunosuppression due to defects in signal transduction in antigen- responsive T cells. The magnitude, prevalence, and prognostic significance of these defects is unclear, due in part to the lack of clinically useful and well-standardized techniques for the assessment of the levels of these signaling protein in T cells. This project will focus on three central components of the T-cell antigen receptor (TCR)- linked signaling cascade. The early component will be monitored by measurements of the CD3-associated zeta chain and Lck. Later elements in the signaling pathway will be NF-kappaB and the nuclear expression of transcription factors involved in the regulation of interferon-gamma synthesis. The specific aims are: (1) to determine the incidence and severity of signal transduction defects in human cancer patients, (2) to correlate abnormalities in signaling proteins with the outcome of immunotherapy protocols, (3) to further develop and validate methods for the quantitation of relevant signal transduction components.